A multiplexed microarray HTS campaign is proposed for a series of proteins relevant to blood coagulation, complement function, neutrophil platelet crosstalk, and lysosomal processes. Protocols are defined where the compound library will be printed in replicate sets on microarrays. Each set of microarrays (3072 compounds/microarray and 33 microarrays per 100,000 compound screen) will be activated with an individual enzyme and a matched fluorogenic substrate. A total of 9 proteases have been fully profiled on microarrays for substrate specificity using 722-member fluorogenic substrate libraries (Ala-P3-P2-K/R libraries). The proposed targets for multiplexed microarray HTS are: Serine proteases (Coagulation) Human factors IXa, Xla, Xa; Serine proteases (Complement) Human C1s, C1r, Factor D; and Human cathepsins (Lysosomal) Cathepsins B, S, G. The use of multiplexed assay on microarrays allows the generation of critical data for the chemical protease interactome.